• Tuberculosis and Respiratory Diseases
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• v.57 no.6
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• pp.557-566
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• 2004

Background : To find out effectiveness of multimodality treatments based on induction chemotherapy(CTx) in patients with clinical stage IIIA NSCLC Methods : From 1997 to 2002, 74 patients with clinical stage IIIA NSCLC underwent induction CTx at the hospital of Chungnam National University. Induction CTx included above two cycles of cisplatin-based regimens(ectoposide, gemcitabine, vinorelbine, or taxol) followed by tumor evaluation. In 30 complete resection group, additional 4500-5000cGy radiotherapy(RTx) was delivered in 15 patients with pathologic nodal metastasis. 29 out of 44 patients who were unresectable disease, refusal of operation, and incomplete resection were followed by 60-70Gy RTx in local treatment. Additional 1-3 cycle CTx were done in case of induction CTx responders in both local treatment groups. Results : Induction CTx response rate were 44.6%(complete remission 1.4% & partial response 43.2%) and there was no difference of response rate by regimens(p=0.506). After induction chemotherapy, only 33 out of resectable 55 ones(including initial resectable 37 patients) were performed by surgical treatment because of 13 refusal of surgery by themselves and 9 poor predicted reserve lung function. There were 30(40.5%) patients with complete resection, 2(2.6%) persons with incomplete resection, and 1(1.3%) person with open & closure. Response rate in 27 ones with chest RTx out of non-operation group was 4.8% CR and 11.9% PR. In complete resection group, relapse free interval was 13.6 months and 2 year recur rate was 52%. In non-complete resection(incomplete resection or non-operation) group, disease progression free interval was 11.2 months and 2 year disease progression rate was 66.7%. Median survival time of induction CTx 74 patients with IIIA NSCLC was 25.1months. When compared complete resection group with non-complete resection group, the median survival time was 31.7 and 23.4months(p=0.024) and the 2-year overall survival rate was 80% and 41%. In the complete resection group, adjuvant postoperative RTx subgroup significantly improved the 2-year local control rate(0% vs. 40%, p= 0.007) but did not significantly improve overall survival(32.2months vs. 34.9months, p=0.48). Conculusion : Induction CTx is a possible method in the multimodality treatments, especially followed by complete resection, but overall survival by any local treatment(surgical resection or RTx) was low. Additional studies should be needed to analysis data for appropriate patient selection, new chemotherapy regimens and the time when should RTx be initiated.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.736-745
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• 1998

Background: Respiratory muscle interaction is further profoundly affected by a number of pathologic conditions. Hyperinflation may be particularly severe in chronic obstructive pulmonary disease(COPD) patients, in whom the functional residual capacity(FRC) often exceeds predicted total lung capacity(TLC). Hyperinflation reduces the diaphragmatic effectiveness as a pressure generator and reduces diaphragmatic contribution to chest wall motion. Ultrasonography has recently been shown to be a sensitive and reproducible method of assessing diaphragmatic excursion. This study was performed to evaluate how differences of diaphragmatic excursion measured by ultrasonography associate with normal subjects and COPD patients. Methods: We measured diaphragmatic excursions with ultrasonography on 28 healthy subjects(l6 medical students, 12 age-matched control) and 17 COPD patients. Ultrasonographic measurements were performed during tidal breathing and maximal respiratory efforts approximating vital capacity breathing using Aloka KEC-620 with 3.5 MHz transducer. Measurements were taken in the supine posture. The ultrasonographic probe was positioned transversely in the midclavicular line below the right subcostal margin. After detecting the right hemidiaphragm in the B-mode the ultrasound beam was then positioned so that it was approximately parallel to the movement of middle or posterior third of right diaphragm. Recordings in the M-mode at this position were made throughout the test. Measurements of diaphragmatic excursion on M-mode tracing were calculated by the average gap in 3 times-respiration cycle. Pulmonary function test(SensorMedics 2800), maximal inspiratory(PImax) and expiratory mouth pressure(PEmax, Vitalopower KH-101, Chest) were measured in the seated posture. Results: During the tidal breathing, diaphragmatic excursions were recorded $1.5{\pm}0.5cm$, $1.7{\pm}0.5cm$ and $1.5{\pm}0.6cm$ in medical students, age-matched control group and COPD patients, respectively. Diaphragm excursions during maximal respiratory efforts were significantly decreased in COPD patients ($3.7{\pm}1.3cm$) when compared with medical students, age-matched control group($6.7{\pm}1.3cm$, $5.8{\pm}1.2cm$, p< 0.05}. During maximal respiratory efforts in control subjects, diaphragm excursions were correlated with $FEV_1$, FEVl/FVC, PEF, PIF, and height. In COPD patients, diaphragm excursions during maximal respiratory efforts were correlated with PEmax(maximal expiratory pressure), age, and %FVC. In multiple regression analysis, the combination of PEmax and age was an independent marker of diaphragm excursions during maximal respiratory efforts with COPD patients. Conclusion: COPD subjects had smaller diaphragmatic excursions during maximal respiratory efforts than control subjects. During maximal respiratory efforts in COPD patients, diaphragm excursions were well correlated with PEmax. These results suggest that diaphragm excursions during maximal respiratory efforts with COPD patients may be valuable at predicting the pulmonary function.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1252-1264
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• 1998

Background : Patients with established ARDS have a mortality rate that exceeds 50 percent despite of intensive care including artificial ventilation modality, Mortality has been associated with sepsis and organ failure preceding or following ARDS ; APACHE II score ; old age and predisposing factors. Revised ventilator strategy over last 10 years especially at ARDS appeared to improve the mortality of it. We retrospectively investigated 40 ARDS patients of respiratory-care unit to examine how these factors influence outcome. Methods : A retrospective investigation of 40 ARDS patients in respiratory-care unit with ventilator management over 46 months was performed. We investigated the clinical characteristics such as a risk factor, cause of death and mortality, and also parameters such as APACHE II score, number of organ dysfunction, and hypoxia score (HS, $PaO_2/FIO_2$) at day 1, 3, 7 of severe acute lung injury, and simultaneously the PEEP level and tidal volume. Results : Clinical conditions associated with ARDS were sepsis 50%, pneumonia 30%, aspiration pneumonia 20%, and mortality rate based on the etiology of ARDS was sepsis 50%, pneumonia 67%(p<0.01 vs sepsis), aspiration pneumonia 38%. Overall mortality rate was 60%. In 28 day-nonsurvivors, leading cause of death was severe sepsis(42.9%) followed by MOF(28.6%), respiratory failure(19.1 %), and others(9.5%). There were no differences in variables of age, sex, APACHE II score, HS, and numbers of organ dysfunction at day 1 of ARDS between 28-days survivor and nonsurvivors. In view of categorized variables of age(>70), APACHE II score(>26), HS(<150) at day 1 of ARDS, there were significant differences between 28-days survivor and nonsurvivors(p<0.05). After day 1 of ARDS, the survivors have improved their APACHE II score, HS, numbers of organ dysfunction over the first 3d to 7d, but nonsurvivors did not improve over a seven-day course. There were significant differences in APACHE II score and numbers of organ dysfunction of day 3, 7 of ARDS, and HS of day 7 of ARDS between survivors and nonsurvivors(p<0.05). Fatality rate of ARDS has been declined from 68% to less than 40% between 1995 and 1998. There were no differences in APACHE II score, HS, numbers of organ dysfunction, old age at presentation of ARDS. In last years, mean PEEP level was significantly higher and mean tidal volume was significantly lower than previous years during seven days of ARDS(p<0.01). Conclusions : Improvement of HS, APACHE II score, organ dysfunction over the first 3d to 7d is associated with increased survival Decline in ARDS fatality rates between 1995 and 1998 seems that this trend must be attributed to improved supportive therapy including at least high PEEP instead of conventional-least PEEP approach in ventilator management of acute respiratory distress syndrome.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1143-1153
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• 1998

Background : Recent outbreaks of pulmonary disease due to drug-resistant strains of Mycobacterium Tuberculosis have resulted in significant morbidity and mortality in patients worldwide. We reviewed our experience to evaluate the effects of pulmonary resection on the management of multidrug-resistant tuberculosis. Method : A retrospective review was performed of 41 patients undergoing pulmonary resection for multidrug-resistant tuberculosis between January 1993 and December 1997. We divided these into 3 groups according to the radiologic findings : (1) patients who have reasonably localized lesion (Localized Lesion Group ; LLG) (2) patients who have cavitary lesions after pulmonary resection on chest roentgenogram (Remained Cavity Group : RCG) (3) patients who have Remained infiltrative lesions postoperatively (Remained infiltrative group : RIG). We evaluated the negative conversion rate after resection and overall response rate of the groups. Then they were compared with the results of the chemotherapy on the multi drug-resistant tuberculosis which has been outcome by Goble et al. Goble et al reported that negative conversion rate was 65% and overall response rate, 56% over a mean period of 5.1 months. Results : Seventy five point six percent were men and 24.4% women with a median age of 31 years (range, 16 to 60 years). Although the patients were treated preoperatively with multidrug regimens in an effort to reduce the mycobacterial burden, 22 of 41 were still sputum culture positive at the time of surgery. 20 of 22 patients(90.9%, p<0.01) responded which is defined as negative sputum cultures within 2 months postoperative. Of 26 patients with the sufficient follow up data, 19 have Remained sputum culture negative for a mean duration of 25.7 months (73.1%, p<0.05). The bulk of the disease was manifest in one lung, but lesser amounts of contralateral disease were demonstrated in 15, consisted of 8 in RIG and 7 in RCG, of 41. 12 of 12 patients (100%, p<0.01) who were sputum positive at the time of surgery in LLG converted successfully. 14 of 15 patients (93.3%, p<0.05) with the follow up have completed treatment and not relapsed for a mean period of 25. 7 months. The mean length of postoperative drug therapy of LLG was 12.2 months. In RIG, postoperative negative conversion rate was 83.3% which was not significant statistically. There was a statistical significance in overall response rate (100%, p<0.05) of RIG for a mean period of 24.4 months with a mean length of postoperative chemotherapy, 11.8 months. In RCG a statistically lower overall response rate (14.3%, p<0.01) has been revealed for a mean duration of follow up, 24.2 months. A negative conversion rate of RCG was 75% which was not significant statistically. Conclusion : Surgery plays an important role in the management of patients with multidrug-resistant Mycobacterium tuberculosis infection. Aggressive pulmonary resection should be performed for resistant Mycobacterium tuberculosis infection to avoid treatment failure or relapse. Especially all cavitary lesions on preoperative chest roentgenogram should be resected completely. If all of them could not be resected perfectly, you should not open the thorax.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.916-924
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• 1996

Bacground : Percutaneous needle aspiration biopsy (PCNA) is one of the most frequently used diagnostic methcxJs for intrathoracic lesions. Previous studies have reponed wide range of diagnostic yield from 28 to 98%. However, diagnostic yield has been increased by accumulation of experience, improvement of needle and the image guiding systems. We analysed the results of PCNA performed for one year to evaluate the diagnostic yield, the rate and severity of complications and factors affecting the diagnostic yield. Method : 287 PCNAs undergone in 236 patients from January, 1994 to December, 1994 were analysed retrospectively. The intrathoracic lesions was targeted and aspirated with 21 - 23 G Chiba needle under fluoroscopic guiding system. Occasionally, 19 - 20 G Biopsy gun was used for core tissue specimen. The specimen was requested for microbiologic, cytologic and histopathologic examination in the case of obtained core tissue. Diagnostic yields and complication rate of benign and malignant lesions were ca1culaled based on patients' chans. The comparison for the diagnostic yields according to size and shape of the lesions was analysed with chi square test (p<0.05). Results : There are 19.9% of consolidative lesion and 80.1% of nodular or mass lesion, and the lesion is located at the right upper lobe in 26.3% of cases, the right middle lobe in 6.4%, the right lower lobe 21.2%, the left upper lobe in 16.8%, the left lower lobe in 10.6%, and mediastinum in 1.3%. The lesion distributed over 2 lobes is as many as 17.4% of cases. There are 74 patients with benign lesions, 142 patients with malignant lesions in final diagnosis and confirmative diagnosis was not made in 22 patients despite of all available diagnostic methods. 2 patients have lung cancer and pulmonary tuberculosis concomittantly. Experience with 236 patients showed that PCNA can diagnose benign lesions in 62.2% (42 patients) of patients with such lesions and malignant lesions in 82.4% (117 patients) of patients. For the patients in whom the first PCNA failed to make diagnosis, the procedure was repeated and the cumulative diagnostic yield was increased as 44.6%, 60.8%, 62.2% in benign lesions and as 73.4%, 81.7%, 82.4% in malignant lesions through serial PCNA. Thoracotomy was performed in 9 patients with benign lesions and in 43 patients with malignant lesions. PCNA and thoracotomy showed the same pathologic result in 44.4% (4 patients) of benign lesions and 58.1% (25 patients) of malignant lesions. Thoracotomy confirmed 4 patients with malignat lesions against benign result of PCNA and 2 patients with benign lesions against malignant result of PCNA. There are 1.0% (3 cases) of hemoptysis, 19.2% (55 cases) of blood tinged sputum, 12.5% (36 cases) of pneumothorax and 1.0% (3 cases) of fever through 287 times of PCNA. Hemoptysis and blood tinged sputum didn't need therapy. 8 cases of pneumothorax needed insertion of classical chest tube or pig-tail catheter. Fever subsided within 48 hours in all cases. There was no difference between size and shape of lesion with diagnostic yield. Conclusion: PCNA shows relatively high diagnostic yield and mild degree complications but the accuracy of histologic diagnosis has to be improved.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.923-933
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• 1995

Background: Pleural abnormality is the the most common respiratory change caused by asbestos dust inhalation and also develop other asbestos related disease after cessation of asbestos exposure. So we conducted epidemiologic study to investigate if the pleural abnormality is associated with pulmonary function change and what factors are influenced on pulmonary function impairment. Methods: Two hundred and twenty two asbestos workers from 9 industries using asbestos in Korea were selected to measure the concentration of sectional asbestos fiber. Ouestionnaire, chest X-ray, PFT were also performed. All the data were analyzed by student t-test and chi-square test using SAS. Regressional analysis was performed to evaluate important factors, for example smoking, exposure concentration, period and the existence of pleural thickening, affecting to the change of pulmonary function. Results: 1) All nine industries except two, airborn asbestos fiber concentration was less than an average permissible concentration. PFT was performed on 222 workers and the percentage of male was 88.3%, their mean age was $41{\pm}9$ years old, and the duration of asbestos exposure was $10.6{\pm}7.8$ yrs. 2) The chest X-ray showed normal(89.19%), pulmonary Tb(inactive)(2.7%), pleral thickening (7.66%), suspected reticulonodular shadow(0.9%). 3) The mean values of height, smoking status, concentration of asbestos fiberwere not different between the subjects with pleural thickening and others, but age, cumulative pack-years, the duration of asbestos exposure were higher in subjects with pleural thickening. 4) All the PFT indices were lower in the subjects with pleural thickening than in the subjects without pleural thickening. 5) Simple regression analysis showed there was a significant correlation between $FEF_{75}$ which is sensitive in small airway obstruction and cumulative smoking pack-years, the duration of asbestos exposure and the concentration of asbestos fiber. 6) Multiple regression analysis showed all the pulmonary function indices were decreased as the increase of cumulative smoking pack-years and especially in the indices those are sensitive in small airway obstruction. Pleural thickening was associated with reduction in FVC, $FEV_1$, PEFR and $FEF_{25}$. Conclusion: The more concentration of asbestos fiber and the more duration of asbestos exposure, the greater reduction in $FEF_{50}$, $FEF_{75}$. Therefore PFT was important in the evaluation of early detection for small airway obstruction. Furthermore pleural thickening without asbesto-related parenchymal lung disease is associated with reduction in pulmonary function.

• Tuberculosis and Respiratory Diseases
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• v.60 no.6
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• pp.653-662
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• 2006

Background: The changes in the pulmonary function observed in burn patients with an inhalation injury are probably the result of a combination of airway inflammation, chest wall and muscular abnormalities, and scar formation. In addition, it appears that prolonged ventilatory support and an episode of pneumonia contribute to the findings. This study investigated the changes in the pulmonary function in patients with inhalation injury at the early and late post-burn periods. Methods: From August 1, 2002, to August 30, 2005, surviving burn patients who had an inhalation injury were enrolled prospectively. An inhalation injury was identified by bronchoscopy within 48hours after admission. Spirometry was performed at the early phase during admission and the recovery phase after discharge, and the changes in the pulmonary function were compared. Results: 37 patients (M=28, F=9) with a total burn surface area (% TBSA), ranging from 0 to 18%, were included. The initial $PaO_2/$FiO_2$ratio and COHb were $286.4{\pm}129.6mmHg$ and $7.8{\pm}6.6%$. Nine cases (24.3%) underwent endotracheal intubation and 3 cases (8.1%) underwent mechanical ventilation. The initial X-ray findings revealed abnormalities in, 18 cases (48.6%) with 15 (83.3%) of these being completely resolved. However, 3 (16.7%) of these had residual sequela. The initial pulmonary function test, showed an obstructive pattern in 9 (24.3%) with 4 (44.4%) of these showing a positive bronchodilator response, A restrictive pattern was also observed in 9 (24.3%) patients. A lower DLco was observed in only 4 (17.4%) patients of which 23 had undergone DLco. In the follow-up study, an obstructive and restrictive pattern was observed in only one (2.7%) case each. All the decreased DLco returned to mormal. Conclusions: Most surviving burn patients with an inhalation injury but with a small burn size showed initial derangements in the pulmonary function test that was restored to a normal lung function during the follow up period.

• Journal of Environmental Health Sciences
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• v.43 no.1
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• pp.1-22
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• 2017

'The worstest environment disaster', 'World's first biocide massacre', 'Home-based Sewol ferry disaster' are all phrases attached to the recent humidifier disinfectant disaster. In the spring of 2011, four of 8 pregnant women including 1 adult man passed away at a university hospital in Seoul due to breathing failure. Epidemiologic investigation conducted by the Korean CDC soon revealed the inhalation of humidifier disinfectant, which had been widely used in Korea during the winter, to be responsible for the disease. As well as lung fibrosis hardening of the lungs, other diseases including asthma, rhinitis, skin disease, liver disease, fetal disease or cancers have been researched for their relation with exposure to the products. By February 9, 2017, 5,342 cases had registered for health problems and 1,131 of them were already dead (20.8% mortality rate). Based on studies by government agencies and a telephone survey of the general population by Seoul National University and civic groups, around 20% of the general public of Korea has used these products. Since the market release of the first product by SK Chemical in 1994, over 7.1 million items from around 20 brands were sold up to 2011. Most of the products were manufactured by well-known large conglomerates such as SK, Lotte, Samsung, Shinsegye, LG, and GS, as well as some European companies including UK-based Reckitt Benckiser and TESCO, the German firm Henkel, the Danish firm KeTox, and an Irish company. Even though this disaster was unveiled in 2011 by the Korean government, the issue of the victims was neglected for over five years. In 2016, an unexpected but intensive investigation by prosecutors found that Reckitt Benckiser manipulated and concealed animal tests for its own brand and brought several university experts and company employees to court. The matter was an intense social issue in Korea from May to June with a surge in media coverage. The prosecutor's investigation and a nationwide boycott campaign organized by victims and environmental groups against Reckitt Benckiser, whose product had been used by more than 70% of victims, led to the producer's official apology and a compensation scheme. A legislative investigation organized after the April 2016 national election revealed the producers' faults and the government's responsibility, but failed to meet expectations. A special law for the victims passed the National Assembly in January 2017 and a punitive system together with a massive environmental epidemiology investigation are expected to be the only solutions for this tragedy. Sciences of medicine, toxicology and environmental health have provided decisive evidence so far, but for the remaining problems the perspectives of social sciences such as sociology and jurisprudence are highly necessary, similar to with the Minamata disease and Wonjin Rayon events. It may not be easy to follow this issue using unfamiliar terminology from medical and chemical science and the long, complicated history of the event. For these reasons the author has attempted to write this article in a question and answer format to render it easier to follow. The 17 questions are: Q1 What is humidifier disinfectant? Q2 What kind of health problems are caused by humidifier disinfectant? Q3 How many victims are there? Q4 What is the analysis of the 1,112 cases of death? Q5 What is the problem with the government's diagnostic criteria and the solution? Q6 Who made what brands? Q7 Has there been a recall? What is still on sale? Q8 Was safety not checked by any producers? Q9 What are the government's responsibilities? Q10 Is it true that these products were sold only in Korea? Q11 Why and how was it unveiled only in 2011 after 17 years of sales? Q12 What delayed the resolution of the victim issue? Q13 What is the background of the prosecutor's investigation in early 2016? Q14 Is it possible to report new victim cases without evidence of product purchase? Q15 What is happening with the victim issue? Q16 How does it compare with the cases of Minamata disease and Wonjin Rayon? Q17 Are there prevention measures and lessons?

• Economic and Environmental Geology
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• v.52 no.6
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• pp.627-635
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• 2019

Cement-asbestos slate is the main asbestos containing material. It is a product made by combining 10~20% of asbestos and cement components. Man- and weathering-induced degradation of the cement-asbestos slates makes them a source of dispersion of asbestos fibres and represents a priority cause of concern. When the asbestos enters the human body, it causes cellular damage or deformation, and is not discharged well in vitro, and has been proven to cause diseases such as lung cancer, asbestos, malignant mesothelioma and pleural thickening. The International Agency for Research on Cancer (IARC) has designated asbestos as a group 1 carcinogen. Currently, most of these slats are disposed in a designated landfill, but the landfill capacity is approaching its limit, and there is a potential risk of exposure to the external environment even if it is land-filled. Therefore, this study aimed to exam the possibility of detoxification of asbestos-containing slate by using exothermic reaction and heat treatment. Cement-asbestos slate from the asbestos removal site was used for this experiment. Exothermic catalysts such as calcium chloride(CaCl₂), magnesium chloride(MgCl₂), sodium hydroxide(NaOH), sodium silicate(Na₂SiO₃), kaolin[Al₂Si₂O₅(OH)₄)], and talc[Mg₃Si₄O₁₀(OH)₂] were used. Six catalysts were applied to the cement-asbestos slate, respectively and then analyzed using TG-DTA. Based on the TG-DTA results, the heat treatment temperature for cement-asbestos slate transformation was determined at 750℃. XRD, SEM-EDS and TEM-EDS analyses were performed on the samples after the six catalysts applied to the slate and heat-treated at 750℃ for 2 hours. It was confirmed that chrysotile[Mg₃Si₂O₅(OH₅)] in the cement-asbestos slate was transformed into forsterite (Mg₂SiO₄) by catalysts and heat treatment. In addition, the change in the shape of minerals was observed by applying a physical force to the slate and the heat treated slate after coating catalysts. As a result, the chrysotile in the cement-asbestos slate maintained fibrous form, but the cement-asbestos slate after heat treatment of applying catalyst was broken into non-fibrous form. Therefore, this study shows the possibility to safely verify the complete transformation of asbestos minerals in this catalyst- and temperature-induced process.

• Journal of Radiation Protection and Research
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• v.37 no.4
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• pp.208-212
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• 2012

In previous studies, ovarian follicle in rat has been used a higher radiation dose than that for cancer radiotherapy in clinical practice. The aim of this study was to evaluate the effect of radiation dose used for cancer radiotherapy on ovarian follicle atresia in rat. Mice of 4-week-old female were whole body irradiated with 2 cGy or 2 Gy (Mevatron 67, Siemens, Germany) and sacrificed by cervical dislocation. Ovaries were collected at 24 hours after irradiation to observe the degree of follicular atresia. Ovaries were fixed in neutral formaldehyde solution for 24 hours and embedded with paraffin. Cutted in $5{\mu}m$ thickness with microtome and stained with hematoxylin and eosin (H&E) and TUNEL immunohistochemical stain, and examined histologically under a light microscope. All data were presented as mean ${\pm}SD$, calculating the ratio of normal or atretic follicles to total ovarian follicles. Statistical analysis was performed by the Mann Whitney test using the SPSS ver 19.0. Ratio of atretic to total follicles of 2 Gy group was significantly higher than control or 2 cGy groups (p<0.05). Ratio of normal to total follicles of 2 Gy group was significantly lower than control group in preantral follicle (64.0 vs. 87.7, p=0.027). Ratio of normal to total follicles of 2 cGy group was significantly increased more than control or 2 Gy groups in antral follicle, and there were no significant difference between control and 2 Gy groups (p=0.522). Radiation dose of 2 Gy for cancer radiotherapy have a significant effect on ovarian follicle atresia in rat.